The retina is a well-organized sensory structure with two main pathways of information transfer. In the vertical pathway photoreceptors sense light and transmit information to bipolar cells, which relay information to ganglion cells, the output of the retina to the brain. Lateral inhibitory pathways, mediated by horizontal cells in the outer retina and amacrine cells in the inner retina, modulate this vertical pathway. Inhibition in the inner retina plays several important roles in retinal signal processing, as it both comprises part of the center-surround receptive field spatial organization of the retina and affects the gain and temporal processing of retinal signaling. Inhibitory inputs come from two distinct amacrine cell sources: GABAergic and glycinergic amacrine cells, and are mediated by three different inhibitory receptors: GABAC, GABAA and glycine receptors. Previous work has suggested that the distributions and kinetics of these inhibitory receptors are important for determining the properties of light-evoked inhibition in the retina. However, little is known about how the neurotransmitter release properties or spatial activation of amacrine cells that provide inhibitory inputs contribute to bipolar cell inhibition. During my mentored research in the lab of Dr. Peter Lukasiewicz, I will determine the role of inhibitory connections between amacrine cells in the spatial regulation of retinal inhibition. For my independent research, I will investigate how distinct neurotransmitter release properties in glycinergic and GABAergic amacrine cells temporally shape inhibition in the retina. Additionally, I will determine if GABAergic and glycinergic amacrine cells, which have distinct spatial extents within the retina, create spatially discrete bipolar cell inhibition. These experiments will determine how the connectivity, release and spatial properties of amacrine cells combine to create the total inhibition in the retina. This will add important knowledge to our understanding of the roles of inhibition in retinal signaling. Additionally, as the retina is an accessible neuronal circuit that can be stimulated physiologically, with light, these experiments will add to our knowledge about how multiple inhibitory inputs contribute to total inhibition in the nervous system. General Statement: To develop approaches to restore normal vision after disease and injury damage the retina, we must first understand how the healthy retina processes visual information. In the proposed research, I will investigate how the properties of modulatory neurons in the retina shape visual signals before they are transmitted to the brain. [unreadable] [unreadable] [unreadable] [unreadable]